The project will investigate the hypothesis that the major histocompatibility complex is one of the key gene systems regulating biologic aging, and that it does so by integrating antibiosenescent properties of the immune system, a number of chemical pathways, particularly the p-450 mixed function oxidases, some DNA-repair mechanisms, and the neuroendocrine system. Existing evidence that all these systems are linked to or influenced by the MHC will be extended in studies of congenic mice and their F1 and F2 hybrids. A program will be developed to investigate the interrelation of MHC genetics and age-related alterations in a variety of functions. These so-called "biomarkers" of aging will include immunological, biochemical and complex physiological function tests applied in both cross-sectional and longitudinal studies, and will require development of micro-methods for the latter. The immunogenetics and other pertinent parameters of the deer mouse (which has a 7-year life span) will be investigated preparatory to comparative and interactive work with the common laboratory mouse (the first task being to establish Peromyscus as a "gerontologic" animal). The project is health related in that it seeks to locate what may be the single genetic basis for aging, and hence for the increasing vulnerability and disease susceptibility that comes with the passage of time in human and animal populations.